P1603: EFFICACY AND SAFETY OF BRUTON’S TYROSINE KINASE INHIBITOR ZANUBRUTINIB IN ITP
Authors: Qiu-Sha Huang, Hai-Xia Fu, Chen-Cong Wang, Xiao-Lu Zhu, Yun He, Qi Chen, Jin Wu, Kai-Yan Liu, Xiao-Jun Huang, Xiao-Hui Zhang
Journal: HemaSphere (2023)

Topic: 32. Platelet disorders Background: Immune thrombocytopenia (ITP) is a severe bleeding disorder. Approximately one-third of ITP patients fail to respond to first-line therapies. In addition, a considerable proportion of patients relapse and require further therapy. The optimal second-line treatment remains a challenge. The role of B cells in the pathogenesis of ITP provides an opportunity to selectively target Bruton tyrosine kinase (BTK) as an effective therapeutic strategy for ITP. Recently, the BTK inhibitor rilzabrutinib has been demonstrated to be effective in ITP (N Engl J Med, 2022). Zanubrutinib is a next-generation BTK inhibitor designed to be more specific and to exert fewer off-target effects than other treatments. The efficacy and safety of zanubrutinib treating ITP were assessed in this phase I, single-arm, open-label trial. Aims: We aimed to evaluate the efficacy and safety of zanubrutinib in patients with corticosteroid-resistant or relapsed ITP. Methods: For this study, patients were enrolled between 1 February, 2022 and 30 December, 2022, at Peking University People’s Hospital. Patients with ITP were eligible to participate in the trial if they were 18 to 70 years of age, had platelet counts lower than 30×109/L on two occasions no less than 7 days apart during the 15 days before enrolling in the trial, and did not achieve a sustained response to treatment with full-dose corticosteroids for a minimum duration of 4 weeks or experienced relapse during steroid tapering or after its discontinuation. All patients received 80 mg of zanubrutinib once daily for 6 weeks. The primary endpoint was overall response (OR), which was defined as at least two consecutive platelet counts of at least 30×109/L, at least a 2-fold increase in the baseline count, the absence of bleeding, and no need for rescue therapy. The trial was registered with ClinicalTrials.gov, number NCT05279872. Results: We enrolled 40 patients between Feb 1, 2022, and Dec 30, 2022. The median age of all the participants was 41.0 (26.0-56.5) years old. A total of 22 (55%, 95% CI, 23-69) patients achieved an overall response to the intervention. Of the 22 patients who achieved OR, 6 received only glucocorticoids, 4 received only TPO-RAs, 2 received only danazol, and 10 received neither. These patients were considered to have had an inadequate response to previous medication at baseline. The median time to response was 13 (IQR 8-42) days, and the median peak platelet count in patients who achieved an overall response was 176×109/L. In all the participants, the mean percentages of weeks with platelet counts of ≥30×109/L and 50×109/L were 31% (95% CI 19%-56%) and 23% (95% CI 13%-43%), respectively. For patients who met the primary endpoint, the mean percentages of weeks with platelet counts of ≥30×109/L and 50×109/L were 60% (95% CI 32%-80%) and 41% (95% CI 23%-65%), respectively. Adverse reactions were, in general, mild. There was no grade 4 or worse adverse events. The most common adverse effects experienced by the patients were upper respiratory tract infections (in 25% of the patients). Four patients (10.0%) experienced a grade 3 upper respiratory tract infection AE. In all the patients, except for infection, the most common adverse effects were diarrhea (20% (n=8)), nausea (15% (n=6)), abdominal distention (10% (n=4)), and increased ALT (10% (n=4)). Summary/Conclusion: Zanubrutinib is an effective and safe treatment for ITP patients with corticosteroid resistance or relapse. This therapy could be a new treatment option for ITP patients. Keywords: Immune thrombocytopenia (ITP), Clinical trial, Bruton’s tyrosine kinase inhibitor (BTKi)